Effect of UV-B Radiation and Desiccation Stress on Photoprotective Compounds Accumulation in Marine Leptolyngbya sp.
Increased awareness regarding the harmful effects of ultraviolet (UV)-B radiation has led to the search for new sources of natural UV-B protecting compounds. Mycosporine-like amino acids are one of such promising compounds found in several organisms. Cyanobacteria are ideal organisms for isolation of these compounds due to their compatibility and adaptability to thrive under harsh environmental conditions. In the following investigation, we report the production of shinorine in Leptolyngbya sp. isolated from the intertidal region. Based on the spectral characteristics and liquid chromatography-mass spectrometry analysis, the UV-absorbing compound was identified as shinorine. To the best of our knowledge, this is the first report on the occurrence of shinorine in Leptolyngbya sp. We also investigated the effect of artificial UV-B radiation and periodic desiccation on chlorophyll-a, total carotenoids, and mycosporine-like amino acids (MAAs) production. The UV-B radiation had a negative effect on growth and chlorophyll concentration, whereas it showed an inductive effect on the production of total carotenoids and MAAs. Desiccation along with UV-B radiation led to an increase in the concentration of photoprotective compounds. These results indicate that carotenoids and MAAs thus facilitate cyanobacteria to avoid and protect themselves from the deleterious effects of UV-B and desiccation.


Implementing a peer-learning approach for the clinical education of respiratory therapy students.
With recent clinical placement demands exceeding supply, the University Health Network (UHN) Respiratory Therapy (RT) department implemented a 2:1 student-to-preceptor model where a focus on peer learning (PL) becomes a key component of program success. PL can be defined as students learning from and with each other in both formal and informal ways. The shift towards facilitative student-directed models in other health care professions can be seen globally with the literature suggesting that 2:1 models not only support increases in student capacity but also improve the student learning experience through PL strategies. The aim of this study was to explore the perceptions of RT preceptors and students regarding the 2:1 model as an educational strategy in the context of their clinical experience. The study further explored experiences of PL to understand how learning is enabled in RT practice-based education, particularly within 2:1 models. A qualitative descriptive study using single-episode semi-structured interviews with RT preceptors (n = 10) and students (n = 10) was conducted during the 2015-2016 RT student clinical year. Twelve open-ended interview questions were designed to draw out study participants' PL experiences and exploration of issues using a 2:1 model in the context of their clinical experience. Data were recorded, transcribed verbatim, and analyzed using thematic analysis. The content analysis resulted in two broad themes with respect to the RT 2:1 educational model: "enablers" and "barriers" to a PL approach. The 2:1 model was preferred by students and preceptors early on in the clinical training due to the benefits of PL, whereas opportunities to showcase independent practice was preferred towards the end of their clinical year. Furthermore, careful planning, resources, and supports need to be implemented to augment benefits and diminish potential disadvantages of using a 2:1 model structure. Participants felt that a 2:1 model strongly contributes to a supportive learning environment and can have a positive influence on the RT student clinical experience at UHN. Along with the improved critical thinking and student engagement opportunities that a 2:1 model offers, increased placement numbers are also supported.


Context-sensitivity of isosteric substitutions of non-Watson-Crick basepairs in recurrent RNA 3D motifs.
Sequence variation in a widespread, recurrent, structured RNA 3D motif, the Sarcin/Ricin (S/R), was studied to address three related questions: First, how do the stabilities of structured RNA 3D motifs, composed of non-Watson-Crick (non-WC) basepairs, compare to WC-paired helices of similar length and sequence? Second, what are the effects on the stabilities of such motifs of isosteric and non-isosteric base substitutions in the non-WC pairs? And third, is there selection for particular base combinations in non-WC basepairs, depending on the temperature regime to which an organism adapts? A survey of large and small subunit rRNAs from organisms adapted to different temperatures revealed the presence of systematic sequence variations at many non-WC paired sites of S/R motifs. UV melting analysis and enzymatic digestion assays of oligonucleotides containing the motif suggest that more stable motifs tend to be more rigid. We further found that the base substitutions at non-Watson-Crick pairing sites can significantly affect the thermodynamic stabilities of S/R motifs and these effects are highly context specific indicating the importance of base-stacking and base-phosphate interactions on motif stability. This study highlights the significance of non-canonical base pairs and their contributions to modulating the stability and flexibility of RNA molecules.


Family planning in Southern India: A survey of women's attitudes.
Women were recruited from villages in the Belgaum district of India. Members of the research team obtained consent and led 58 interviews in the local languages. Participants were asked questions covering topics related to postpartum contraceptive counseling, knowledge, and experience; postpartum sexual practice; birth spacing desire and counseling; and interest in long-acting reversible contraceptives (LARCs). Women generally desired 3 years of birth spacing. A majority did not receive counseling regarding postpartum contraception during the prenatal period, although most would have liked to have received such counseling. Those who had made a contraceptive plan during the prenatal period had an odds ratio of 25.2 (95% CI 4.9-128.6, p = 0.00001) for using postpartum contraception. Influences on contraceptive decisions primarily came from friends and family, while information from medical providers was not a major influence. Most women did not believe they could make their own decisions regarding contraception use, but those who did had an adjusted odds ratio of 56 (95% CI 3.4-9161, p = 0.0047) of utilizing postpartum contraception. Women generally liked the idea of LARCs. A large majority of the women surveyed (89.66%) liked the idea of a subdermal contraceptive implant, a method currently unavailable in this region. Ultimately, the women surveyed do have healthy attitudes and goals regarding birth spacing but few utilize effective contraception in order to meet their goals. Further efforts in counseling as well as availability of a wider variety of contraceptive methods, including the subdermal contraceptive implant, may decrease the disparity between desires and practices.


Stereotaxic probabilistic maps of the magnocellular cell groups in human basal forebrain.
The basal forebrain contains several interdigitating anatomical structures, including the diagonal band of Broca, the basal nucleus of Meynert, the ventral striatum, and also cell groups underneath the globus pallidus that bridge the centromedial amygdala to the bed nucleus of the stria terminalis. Among the cell populations, the magnocellular, cholinergic corticopetal projection neurons have received particular attention due to their loss in Alzheimer's disease. In MRI images, the precise delineation of these structures is difficult due to limited spatial resolution and contrast. Here, using microscopic delineations in ten human postmortem brains, we present stereotaxic probabilistic maps of the basal forebrain areas containing the magnocellular cell groups. Cytoarchitectonic mapping was performed in silver stained histological serial sections. The positions and the extent of the magnocellular cell groups within the septum (Ch1-2), the horizontal limb of the diagonal band (Ch3), and in the sublenticular part of the basal forebrain (Ch4) were traced in high-resolution digitized histological sections, 3D reconstructed, and warped to the reference space of the MNI single subject brain. The superposition of the cytoarchitectonic maps in the MNI brain shows the intersubject variability of the various Ch compartments and their stereotaxic position relative to other brain structures. Both the right and left Ch4 regions showed significantly smaller volumes when age was considered as a covariate. Probabilistic maps of compartments of the basal forebrain magnocellular system are now available as an open source reference for correlation with fMRI, PET, and structural MRI data of the living human brain.


[Vitronectin: mediator of cell adhesion in proliferative vitreoretinopathy?].
Vitronectin, also known as protein S, the "serum spreading factor", or epibolin, was detected as an essential mediator of adhesion and spreading in many cells in vitro. The relatively low molecular weight of 65 kDa and a high plasma level of 200 mg/l implicate vitronectin as a possibly important factor in the pathogenesis of proliferative vitreoretinopathy (PVR) which is characterized by a breakdown of blood-ocular barriers. In a study of 15 periretinal membranes, using double label immunofluorescence techniques, we found vitronectin to be a significant component of the specimens' extracellular matrix in 13 cases. Vitronectin is co-localized with fibronectin, a much larger glycoprotein suggested as being involved in the pathogenesis of PVR. Among the biological properties of fibronectin are a role in cellular migration, adhesion, and proliferation. Both proteins share a unique cell recognition amino acid sequence, which mediates the receptor-dependent interaction between the extracellular matrix macromolecules and proliferating cells. Plasma is suggested as the major source of vitronectin in PVR because vitronectin could be detected in vitreous aspirates from patients with PVR, using electrophoresis and immunoblotting, but not in physiological human vitreous.


The ethics of hormesis--no fuss?
It has been argued that the phenomenon of hormesis should prompt us to revise current regulatory policy in order to take beneficial effects of small doses of various agents into account. I argue that three problems--the comparative smallness of hormetic effects, the fine-tuning problem, and the problem of aggregated actions--should lead us not to overemphasize the importance of hormesis for policy, and that they, if anything, points towards a non-consequentialist approach to the ethics of risk.


Measuring Survival of Adherent Cells with the Colony-Forming Assay.
Measuring cell death with colorimetric or fluorimetric dyes such as trypan blue and propidium iodide (PI) can provide an accurate measure of the number of dead cells in a population at a specific time; however, these assays cannot be used to distinguish cells that are dying or marked for future death. In many cases it is essential to measure the proliferative capacity of treated cells to provide an indirect measurement of cell death. This can be achieved using the colony-forming assay described here. This protocol specifically applies to measurement of HeLa cells but can be used for most adherent cell lines with limited motility.


Mouthwashes: Implications for Practice.
This is the concluding article in the supplement on the role of mouthwashes in oral care, which summarises the current guidelines across the globe regarding their acceptable adjunctive use for managing caries, gingivitis, and periodontal disease. Based on moderate evidence for clinical effectiveness, most current guidelines suggest fluoride mouthwashes for the management of dental caries, and chlorhexidine for the management of periodontal diseases. However there still appears to be gaps in the literature underpinning these recommendations. Importantly, all evidence supports such mouthwash use "adjunctively," alongside mechanical oral hygiene measures. Other antimicrobial mouthwashes such as essential oils and cetylpyridinium chloride may also be clinically effective against plaque and gingivitis, but there is a current lack of robust evidence of natural mouthwashes to recommend their adjunctive use. The authors of the current review are of the view that mouthwashes may not be of much value in those with good periodontal health or low caries risk. The reasons for this are, the potential i) risks of allergic reactions, ii) dysbiosis of the oral microbiota, iii) emergence of antimicrobial resistance, and iv) deleterious effects on the environment. There is, however, much empirical research needed on mouthwashes, particularly in vivo research derived through clinical trials. Thus, dental practitioners need to keep abreast of the evidence base on the current, and the emerging, over-the-counter mouthwashes, and pay heed to the consensus views emanating from systematic reviews, as well as international guidelines on mouthwashes.


Targeting a novel bone degradation pathway in primary bone cancer by inactivation of the collagen receptor uPARAP/Endo180.
In osteosarcoma, a primary mesenchymal bone cancer occurring predominantly in younger patients, invasive tumour growth leads to extensive bone destruction. This process is insufficiently understood, cannot be efficiently counteracted and calls for novel means of treatment. The endocytic collagen receptor, uPARAP/Endo180, is expressed on various mesenchymal cell types and is involved in bone matrix turnover during normal bone growth. Human osteosarcoma specimens showed strong expression of this receptor on tumour cells, along with the collagenolytic metalloprotease, MT1-MMP. In advanced tumours with ongoing bone degeneration, sarcoma cells positive for these proteins formed a contiguous layer aligned with the degradation zones. Remarkably, osteoclasts were scarce or absent from these regions and quantitative analysis revealed that this scarcity marked a strong contrast between osteosarcoma and bone metastases of carcinoma origin. This opened the possibility that sarcoma cells might directly mediate bone degeneration. To examine this question, we utilized a syngeneic, osteolytic bone tumour model with transplanted NCTC-2472 sarcoma cells in mice. When analysed in vitro, these cells were capable of degrading the protein component of surface-labelled bone slices in a process dependent on MMP activity and uPARAP/Endo180. Systemic treatment of the sarcoma-inoculated mice with a mouse monoclonal antibody that blocks murine uPARAP/Endo180 led to a strong reduction of bone destruction. Our findings identify sarcoma cell-resident uPARAP/Endo180 as a central player in the bone degeneration of advanced tumours, possibly following an osteoclast-mediated attack on bone in the early tumour stage. This points to uPARAP/Endo180 as a promising therapeutic target in osteosarcoma, with particular prospects for improved neoadjuvant therapy.


A hybrid phantom Monte Carlo-based method for historical reconstruction of organ doses in patients treated with cobalt-60 for Hodgkin's lymphoma.
Historical radiotherapy treatment plans lack 3D images sets required for estimating mean organ doses to patients. Alternatively, Monte Carlo-based models of radiotherapy devices coupled with whole-body computational phantoms can permit estimates of historical in-field and out-of-field organ doses as needed for studies associating radiation exposure and late tissue toxicities. In recreating historical patient treatments with 60Co based systems, the major components to be modeled include the source capsule, surrounding shielding layers, collimators (both fixed and adjustable), and trimmers as needed to vary field size. In this study, a computational model and experimental validation of the Theratron T-1000 are presented. Model validation is based upon in-field commissioning data collected at the University of Florida, published out-of-field data from the British Journal of Radiology (BJR) Supplement 25, and out-of-field measurements performed at the University of Wisconsin's Accredited Dosimetry Calibration Laboratory (UWADCL). The computational model of the Theratron T-1000 agrees with central axis percentage depth dose data to within 2% for 6 × 6 to 30 × 30 cm2 fields. Out-of-field doses were found to vary between 0.6% to 2.4% of central axis dose at 10 cm from field edge and 0.42% to 0.97% of central axis dose at 20 cm from the field edge, all at 5 cm depth. Absolute and relative differences between computed and measured out-of-field doses varied between ±2.5% and ±100%, respectively, at distances up to 60 cm from the central axis. The source-term model was subsequently combined with patient-morphometry matched computational hybrid phantoms as a method for estimating in-field and out-of-field organ doses for patients treated for Hodgkin's Lymphoma. By changing field size and position, and adding patient-specific field shaping blocks, more complex historical treatment set-ups can be to recreated, particularly those for which 2D or 3D image sets are unavailable.


Relationship Between Effort-Reward Imbalance, Over-Commitment and Occupational Burnout in the General Population: A Prospective Cohort Study.
Objectives: To prospectively investigate the association between Effort-Reward Imbalance (ERI) and over-commitment and the scores of the burnout dimensions over a 4 years follow-up period considering potential confounders. Methods: Data stemmed from CoLaus|PsyCoLaus, a population-based cohort study including 575 participants (mean age 55 years, 50% men). Participants completed the Maslach Burnout Inventory-General Survey, ERI and over-commitment questionnaires at baseline (T1) and after a 4 years follow-up (T2), and provided demographic, behavioral, psychiatric, personality and social support information through self-reported questionnaires and semi-structured interviews. Serially adjusted linear regression models were used. Results: ERI and over-commitment were not associated longitudinally with any of the burnout dimensions when controlling for confounders. One standard deviation increases in the scores of exhaustion, cynicism and professional efficacy were associated with one standard deviation increase in the scores of the same burnout dimensions longitudinally, and these associations were independent of the effects of ERI and over-commitment. Conclusion: Future studies should re-examine the effect of ERI and over-commitment on workers' burnout, considering the effects of confounders.


Computer modeling of polyleucine-based coiled coil dimers in a realistic membrane environment: insight into helix-helix interactions in membrane proteins.
Simulated annealing was performed to model parallel dimers of alpha-helical transmembrane peptides with the sequence L(11)XL(12), predicting left-handed coiled coil geometry in all cases. Insertion of peptides containing threonine, asparagine, alanine, phenylalanine, and leucine in position 12 into realistic model membranes showed these structures were stable for 20 ns of molecular dynamics simulation time. Threonine could participate in intermolecular hydrogen bonds, but predominantly formed hydrogen bonds to the backbone of the helix it resided on. These hydrogen bonds, although infrequent, appeared to promote closer association of polyleucine helices. Asparagine participated in multiple, rapidly fluctuating intermolecular and intramolecular hydrogen bonds, and may have slightly destabilized optimum van der Waals packing in favor of optimum hydrogen bonding. Coordinated rotations of transmembrane helices about their axes were observed, indicating helices may rotate around one another during the folding of membrane proteins or other processes. These rotations were inhibited by phenylalanine, suggesting a role for bulky residues in modulating membrane protein dynamics.


OUTCOMES OF SURGERY IN PROLIFERATIVE VITREORETINOPATHY.
To present the anatomical and functional outcomes of surgery in cases of rhegmatogenous retinal detachment complicated (at presentation) by proliferative vitreoretinopathy (PVR). Retrospective study of the cases operated upon by a single surgeon between October 2012 and September 2014. A total of 49 eyes of 49 patients had PVR at presentation (12 cases with PVR stage B, 21 with stage C and 16 with stage D). 82% had a VA < or = 0.05 at presentation. Peripheral retinectomy was the primary surgery in 57% of cases. Reinterventions was required in 16.3% of the cases (silicon oil extraction was not considered reintervention). Although at the first postoperative examination 32% of eyes had an IOP > 21 mmHg without medication, only 8% retained a high lOP at the last visit. At the last visit 73.4% of eyes presented attached retina (an additional 6% had an attached macula under silicone oil, but sub retinal fluid in the inferior quadrants). A final VA > or = 0.05 was recorded in 67.3% of eyes (of which half had VA > or = 0.1) CONCLUSIONS: In cases presenting with retinal detachment complicated by PVR the possibility of reinterventions and the risk of intraocular hypertension should be considered. Unfortunately, even some cases with favorable anatomical outcome will not present ambulatory vision. Keywords:


[Development of MEDUC-PG14 survey to assess postgraduate teaching in medical specialties].
Feedback is one of the most important tools to improve teaching in medical education. To develop an instrument to assess the performance of clinical postgraduate teachers in medical specialties. A qualitative methodology consisting in interviews and focus-groups followed by a quantitative methodology to generate consensus, was employed. After generating the instrument, psychometric tests were performed to assess the construct validity (factor analysis) and reliability (Cronbach's alpha). Experts in medical education, teachers and residents of a medical school participated in interviews and focus groups. With this information, 26 categories (79 items) were proposed and reduced to 14 items (Likert scale 1-5) by an expert's Delphi panel, generating the MEDUC-PG14 survey, which was answered by 123 residents from different programs of medical specialties. Construct validity was carried out. Factor analysis showed three domains: Teaching and evaluation, respectful behavior towards patients and health care team, and providing feedback. The global score was 4.46 ± 0.94 (89% of the maximum). One teachers' strength, as evaluated by their residents was "respectful behavior" with 4.85 ± 0.42 (97% of the maximum). "Providing feedback" obtained 4.09 ± 1.0 points (81.8% of the maximum). MEDUC-PG14 survey had a Cronbach's alpha coefficient of 0.947. MEDUC-PG14 survey is a useful and reliable guide for teacher evaluation in medical specialty programs. Also provides feedback to improve educational skills of postgraduate clinical teachers.


Phosphate test 2.0.
The accurate measurement of the phosphate content of a liposomal suspension is important when working with differential scanning calorimetry. Standard phosphate tests date back several decades and require extended hands-on time. Here, we present a rapid version of a phosphate test taking advantage of microwave-assisted chemical digestion and multiwell plate reading technology allowing for the fast and accurate testing of many samples in parallel.


Assessment of a Private Payer Bundled Payment Model for Lumbar Decompression Surgery.
Although bundled payment models are well-established in Medicare-aged individuals, private insurers are now developing bundled payment plans. The role of these plans in spine surgery has not been evaluated. Our objective was to analyze the performance of a private insurance bundled payment program for lumbar decompression and microdiskectomy. A retrospective review was conducted of all lumbar decompressions in a private payer bundled payment model at a single institution from October 2018 to December 2020. 120-day episode of care cost data were collected and reported as net profit or loss regarding set target prices. A stepwise multivariable linear regression model was developed to measure the effect of patient and surgical factors on net surplus or deficit. Overall, 151 of 468 (32.2%) resulted in a deficit. Older patients (58.6 vs. 50.9 years, P < 0.001) with diabetes (25.2% vs. 13.9%, P = 0.004), hypertension (38.4% vs. 28.4%, P = 0.038), heart disease (13.9% vs. 7.57%, P = 0.030), and hyperlipidemia (51.7% vs. 35.6%, P = 0.001) were more likely to experience a loss. Surgically, decompression of more levels (1.91 vs. 1.19, P < 0.001), posterior lumbar decompression (86.8% vs. 56.5%, P < 0.001), and performing surgery at a tertiary hospital (84.8% vs. 70.3%, P < 0.001) were more likely to result in loss. All readmissions resulted in a loss (4.64% vs. 0.0%, P < 0.001). On multivariable regression, microdiskectomy (β: $2,398, P = 0.012) and surgery in a specialty hospital (β: $1,729, P = 0.096) or ambulatory surgery center (β: $3,534, P = 0.055) were associated with cost savings. Increasing number of levels, longer length of stay, active smoking, and history of cancer, dementia, or congestive heart failure were all associated with degree of deficit. Preoperatively optimizing comorbidities and using risk stratification to identify those patients who may safely undergo surgery at a facility other than an inpatient hospital may help increase cost savings in a bundled payment model of working-age and Medicare-age individuals.


Irreversible thiol oxidation in carbonic anhydrase III: protection by S-glutathiolation and detection in aging rats.
Proteins with reactive sulfhydryls are central to many important metabolic reactions and also contribute to a variety of signal transduction systems. In this report, we examine the mechanisms of oxidative damage to the two reactive sulfhydryls of carbonic anhydrase III. Hydrogen peroxide (H2O2), peroxy radicals, or hypochlorous acid (HOCl) produced irreversibly oxidized forms, primarily cysteine sulfinic acid or cysteic acid, of carbonic anhydrase III if glutathione (GSH) was not present. When GSH was approximately equimolar to protein thiols, irreversible oxidation was prevented. H202 and peroxyl radicals both generated S-glutathiolated carbonic anhydrase III via partially oxidized protein sulfhydryl intermediates, while HOCl did not cause S-glutathiolation. Thus, oxidative damage from H202 or AAPH was prevented by protein S-glutathiolation, while a direct reaction between GSH and oxidant likely prevents HOCl-mediated protein damage. In cultured rat hepatocytes, carbonic anhydrase III was rapidly S-glutathiolated by menadione. When hepatocyte glutathione was depleted, menadione instead caused irreversible oxidation. We hypothesized that normal depletion of glutathione in aged animals might also lead to an increase in irreversible oxidation. Indeed, both total protein extracts and carbonic anhydrase III contained significantly more cysteine sulfinic acid in older rats compared to young animals. These experiments show that, in the absence of sufficient GSH, oxidation reactions lead to irreversible protein sulfhydryl damage in purified proteins, cellular systems, and whole animals.


Investigating the Nexus between Gynaecologic Cancer and Human Development Index.
This study aimed to describe the current incidence and mortality rates of gynecologic cancer and their association with socio- economic development. The data for the age-standardized incidence rate (ASRI) and age-standardized mortality rate (ASRM) were acquired from the GLOBOCAN-2012 database. Human Development Index (HDI) data were obtained from the 2015- Human Development Report. The correlation between HDI and Mortality to Incidence Ratio (MIR) was assessed by Pearson- correlation. The effect of national-HDI on MIR was analyzed by linear regression analysis. The ASRI, ASRM, and MIR of cervix cancer were higher in the less developed regions (LDRs) than in more developed regions (MDRs). However, for corpus uteri cancer, the ASRI was 3.6 times and the ASRM was 1.5-times higher in the MDRs than in the LDRs. Strong inverse associations between MIR and HDI were reported from cervix (adjusted R2 = 0.825, β = - 0.908, p < 0.001), corpus uteri (adjusted R2 = 0.554, β = - 0.746, p < 0.001) and ovarian cancer (adjusted R2 = 0.579, β = - 0.763, p < 0.001). The higher MIR of gynecologic cancer in LDRs demand for sustainable investment in health systems and balanced cancer control plans in the region.


Incidence of phantom limb phenomena after lower limb amputations in a Singapore tertiary hospital.
Phantom limb sensations (PLS), phantom limb pain (PLP) and stump pain (SP) are well-recognised postamputation phenomena. However, there is a dearth of related epidemiological data in Asian populations. This study was conducted to fill the information gap. Telephone interviews were conducted with patients who underwent lower limb amputations at a tertiary hospital in Singapore. Information was obtained on phantom limb characteristics, perioperative pain and functional assessment. A total of 159 patients underwent amputations over a 31-month period. At the time of the interview, 47 patients had died and 66 were contactable, of whom 49 patients were interviewed. Of these, 31 (63%) patients experienced PLS. 22 patients had postoperative pain, with 9 having both PLP and SP, 3 having PLP alone and 10 having SP alone. Among the 12 patients with PLP, at least 6 (50%) experienced constant or daily pain and 7 (58%) scored their pain as moderate-to-severe. Among those with PLP and/or SP (n = 22), 5 were distressed by the pain, 11 were on analgesics and 3 received medical follow-up. 7 (32%) patients reported functional limitations secondary to PLP or SP. Altogether, 28 (57%) patients were wheelchair or bed bound. The incidence of PLP was 25% in our cohort. Although this is lower than that reported in other studies, it remains significant, as some patients suffered moderate-to-severe pain. The difference in incidence may be due to differences in the ethnic composition and/or indications for amputation in our group. Follow-up and care could improve the outcomes in these patients.


Topical Treatment of Persistent Epithelial Defects with a Matrix Regenerating Agent.
The aim of the study was to assess the efficacy of a topical regenerating agent (RGTA) for management of persistent epithelial defects (PEDs) resistant to conventional therapy. Twenty-one patients (23 eyes) with PEDs despite the use of conventional therapy for lagophthalmos (n = 4), neurotrophic ulcer (n = 9), chemical burn (n = 3), Stevens-Johnson syndrome (n = 1), atopic keratoconjunctivitis (n = 1), severe dry eye (n = 2), peripheral ulcerative keratitis (n = 1), fungal keratitis (n = 1), and bacterial keratitis (n = 1) were enrolled in the study. Patients were treated with RGTA (Cacicol; Thea, Paris, France) instilled at a dosage of one drop on alternate days. Patients were evaluated by slit-lamp examination, anterior segment photography, and fluorescein-dye testing. Ulcer areas were noted on alternate days starting from the first day of instillation. Twenty of 23 eyes (86.9%) displayed complete corneal healing after a mean period of ∼7.2 days (range, 2-20 days). Mean decrease ratio of ulcer area observed was 61.2% (range, 8.8%-100%, n = 19) on the 2nd day, 74.4% (range, 36%-100%, n = 16) on the 4th day, 80.2% (range, 43.7%-100%, n = 12) on the 6th day, 88.5% (range, 55.9%-100%, n = 9) on the 8th day, and 85.5% (range, 58.3%-100%, n = 7) on the 10th day. No significant differences were found in the epithelialization speed between eyes with and without bandage contact lenses in any postoperative day (P > 0.05). There were no treatment-related local or systemic side effects during the study. RGTA seems to be an effective therapeutic alternative in the treatment of persistent corneal epithelial defects.


Plakophilin 2 affects cell migration by modulating focal adhesion dynamics and integrin protein expression.
Plakophilin 2 (PKP2), a desmosome component, modulates the activity and localization of the small GTPase RhoA at sites of cell-cell contact. PKP2 regulates cortical actin rearrangement during junction formation, and its loss is accompanied by an increase in actin stress fibers. We hypothesized that PKP2 may regulate focal adhesion dynamics and cell migration. Here we show that PKP2-deficient cells bind efficiently to the extracellular matrix, but upon spreading display total cell areas ≈ 30% smaller than control cells. Focal adhesions in PKP2-deficient cells are ≈ 2 × larger and more stable than in control cells, and vinculin displays an increased time for fluorescence recovery after photobleaching. Furthermore, β4 and β1 integrin protein and mRNA expression is elevated in PKP2-silenced cells. Normal focal adhesion phenotypes can be restored in PKP2-null cells by dampening the RhoA pathway or silencing β1 integrin. However, integrin expression levels are not restored by RhoA signaling inhibition. These data uncover a potential role for PKP2 upstream of β1 integrin and RhoA in integrating cell-cell and cell-substrate contact signaling in basal keratinocytes necessary for the morphogenesis, homeostasis, and reepithelialization of the stratified epidermis.


Shared Medical Decision Making in Lung Cancer Screening: Experienced versus Descriptive Risk Formats.
Annual lung cancer screening using low-dose computed tomography (LDCT) scans is associated with a survival benefit, but it is also associated with potential harm. Unlike descriptive probability formats, experienced tasks have been shown to decrease perceptions of rare events. The objective of this study was to compare descriptive versus experienced probability formats on patients' knowledge, beliefs, endorsement of screening for heavy smokers, and preference (choice predisposition) to undergo screening. A total of 276 patients attending an outpatient pulmonary practice were randomized to learn about screening using 1 of 3 formats: numbers only, numbers + icon arrays, numbers + a set of slides illustrating LDCT scans of 250 people in random order that displayed the number of normal scans, false-positive lung nodules, cancers found leading to a life saved, and cancers found leading to death despite treatment. Knowledge differed between the 3 formats (P= 0.001), with participants randomized to the numbers + icon array format having the highest knowledge score. Beliefs were more favorable among participants randomized to the numbers + experienced format compared with the numbers + icon array format (difference between means [95% confidence interval]= 1.6 [0.4-2.8]). Differences in participants' endorsement of screening (P= 0.4) and choice predisposition (P= 0.6) across probability format mirrored those of beliefs but were not statistically significant. Contrary to what we expected, the experienced format increased propensity toward screening compared with the numbers + icon array format, as indicated by more favorable beliefs and nonsignificant trends toward stronger choice predisposition and endorsement. Experienced risk formats may not be a practical approach to improve risk communication for patients deciding whether or not to undergo annual lung cancer screening.


[The effect of narcotic analgesics on the central nervous system as an index of their drug addiction potential].
The relationship between the average effective doses causing disturbances of the statokinetic reflex and the average effective doses of the analgesic and hyperthermic actions of morphine, fentanyl, codeine and tilidine was studied in the experiments on Wistar rats. The effective analgesic and hyperthermic doses of morphine (the agent with the highest drug-addiction properties) approach the dose inducing coordination disorders. In this respect fentanyl and codeine are close to morphine. The effective doses of tilidine (the agent with the lowest drug-addiction properties among the studied agents) possess significant differences. The importance of the relationship between the mentioned effective doses and the drug-addiction properties of the analgesics.


A fructan, from Radix ophiopogonis, stimulates the proliferation of cultured lymphocytes: structural and functional analyses.
A fructan, Opaw-2, with molecular mass of about 14 kDa, was isolated from the tuberous roots of Ophiopogon japonicus. Opaw-2 comprises fructose and glucose with a molar ratio of 30:1. Linkage and NMR analyses indicated that Opaw-2 has a backbone structure of beta-(1-->2)-Fruf and beta-(2-->6)-Fruf residues that branches at O-6 of beta-(1-->2)-Fruf residues with alpha-1-linkage to the Glcp residues and terminates with Fruf residues. In cultured lymphocytes, the application of Opaw-2 significantly stimulated the proliferation of lymphocytes in a dose-dependent manner. By using atomic force microscopy, Opaw-2 showed a morphological change from globular to helical fibrous shape at increasing concentrations.


Correlation between Very Short and Short-Term Blood Pressure Variability in Diabetic-Hypertensive and Healthy Subjects.
Blood pressure (BP) variability can be evaluated by 24-hour ambulatory BP monitoring (24h-ABPM), but its concordance with results from finger BP measurement (FBPM) has not been established yet. The aim of this study was to compare parameters of short-term (24h-ABPM) with very short-term BP variability (FBPM) in healthy (C) and diabetic-hypertensive (DH) subjects. Cross-sectional study with 51 DH subjects and 12 C subjects who underwent 24h-ABPM [extracting time-rate, standard deviation (SD), coefficient of variation (CV)] and short-term beat-to-beat recording at rest and after standing-up maneuvers [FBPM, extracting BP and heart rate (HR) variability parameters in the frequency domain, autoregressive spectral analysis]. Spearman correlation coefficient was used to correlate BP and HR variability parameters obtained from both FBPM and 24h-ABPM (divided into daytime, nighttime, and total). Statistical significance was set at p < 0.05. There was a circadian variation of BP levels in C and DH groups; systolic BP and time-rate were higher in DH subjects in all periods evaluated. In C subjects, high positive correlations were shown between time-rate index (24h-ABPM) and LF component of short-term variability (FBPM, total, R = 0.591, p = 0.043); standard deviation (24h-ABPM) with LF component BPV (FBPM, total, R = 0.608, p = 0.036), coefficient of variation (24h-ABPM) with total BPV (FBPM, daytime, -0.585, p = 0.046) and alpha index (FBPM, daytime, -0.592, p = 0.043), time rate (24h-ABPM) and delta LF/HF (FBPM, total, R = 0.636, p = 0.026; daytime R = 0,857, p < 0.001). Records obtained from DH showed weak positive correlations. Indices obtained from 24h-ABPM (total, daytime) reflect BP and HR variability evaluated by FBPM in healthy individuals. This does not apply for DH subjects.


Optimal intake of clear liquids during preparation for afternoon colonoscopy with low-volume polyethylene glycol plus ascorbic acid.
The standard colonoscopy preparation regimen in Japan for afternoon procedures is sequential intake of 1 L of polyethylene glycol electrolyte lavage solution containing ascorbic acid (PEG-ASC), 0.5 L of clear liquid, 0.5 L of PEG-ASC, and finally 0.25 L of clear fluids (all at a rate of 0.25 L every 15 min). However, this regimen seems poorly tolerated and complicated for many patients compared to previous regimen of polyethylene glycol electrolyte lavage solution. The aim of this study was to evaluate an alternate regimen of 0.5 L of PEG-ASC followed by 0.25 L clear liquids, repeated 3 times. This was a single-blinded, non-inferiority, randomized controlled study. Subjects were randomized to the standard regimen or the alternate regimen using a web-based registry system. All patients were instructed to eat a pre-packaged, low residue diet and to take sodium picosulfate hydrate the day before colonoscopy. The Boston Bowel Preparation Scale was used to evaluate bowel cleansing, and a 3-point scale was used to assess mucosal visibility. The primary endpoint was successful bowel cleansing. The acceptability, tolerability, safety, and endoscopic findings of these two regimens were secondary endpoints. A total of 409 patients were randomized to either the standard regimen (n = 204, males 54.0 %, mean age 65.5 years) or the alternate regimen (n = 205, 54.6 %, 65.0 years). The rates of successful bowel cleansing were 71.1 % (64.3 - 77.2 %) with the standard regimen vs. 75.1 % (68.6 - 80.9 %) with the alternate regimen (95 % lower confidence limit, for the difference = - 4.6, non-inferiority P < 0.05). No significant differences were found in tolerability, safety, and endoscopic findings. The alternate regimen and standard regimen are clinically equivalent with respect to cleansing efficacy and acceptability, tolerability, safety, and endoscopic findings. These results are good news for patients with difficulty drinking the first liter of PEG-ASC.


Trial of an asthma action plan in the Maori community of the Wairarapa.
An asthma action plan has been tested in a study conducted by Wairarapa Maori community health workers and the Wellington asthma research group. There were several distinctive features of the project, including the programme of marae-based asthma clinics, and the partnership between the researchers and the Maori community groups. This paper describes the process by which the study was conducted since this experience may be relevant to future Maori health research projects. The programme was launched with a series of hui at marae in the Wairarapa, and marae-based clinics were set up. These were followed up by further support from the Maori community health workers who helped people to keep diaries to monitor their asthma, and generally maintained contact. The severity of asthma in the participants was compared for a two-month period before the action plan was introduced, and for a four-month period after the plan was introduced. There was a high participation rate, with 91% (63/69) of participants finishing the programme, 75% of whom adequately completed their daily asthma diaries. Asthma control improved significantly in the participants. They commented positively on the programme, and particularly on the marae-based clinics. The study was successful in terms of participation in the marae-based clinics, acceptance and use of the plan, and improvement in asthma control of the participants. The findings indicate what can be achieved when researchers and Maori community groups work in partnership.


Preoperative Ultrasonography as a Predictor of Difficult Laparoscopic Cholecystectomy that Requires Conversion to Open Procedure.
The present study was conducted to see whether preoperative ultrasonography can be used as a predictor of difficult lapariscopic cholecystectomy or not. 50 patients of cholelithiasis, selected from surgical OPD of Rajindra Hospital Patiala, who fulfilled all inclusion and exclusion criteria for the study underwent elective cholecystectomy. Ultrasonography was done pre-operatively on all cases in the same setup and with same probe and patients underwent laparoscopic cholecystectomy in same setup. A significant prediction was found between ultrasonographic parameters and conversion of the procedure to open cholecystectomy which proved that pre-operative ultrasonography is a good predictor of difficulty in laparoscopic cholecystectomy in majority of the cases and should be used as a screening procedure. Preoperative ultrasonography should be used as a screening procedure as it is a good predictor of difficulty in laparoscopic cholecystectomy in majority of the cases. It can help surgeon to get an idea of potential difficulty that he can face in the particular patient.


Micro-Raman Spectroscopy for the Determination of Local Temperature Increases in TiO2 Thin Films due to the Effect of Radiation.
This study applied a classic method involving Raman spectroscopy and the use of Stokes and anti-Stokes peaks to measure the temperature of TiO2 thin films found in dye-sensitized solar cells (DSSCs). In addition, three mathematical formulae were used and analyzed to estimate the increase in temperature generated solely by the effect of the radiation. The tests and calculations performed showed an increase in the temperature of the TiO2 film. That is, the films were heated by the radiation they were exposed to. A temperature increase of up to 30 K was detected for the sample with a single layer of TiO2, and over 40 K for the sample with three layers for the highest radiation powers used, and greater increases in temperature were observed in the thicker films.


Process of the development of T-2 toxin-induced apoptosis in the lymphoid organs of mice.
Female ICR:CD-1 mice orally treated with 10 mg/kg b.w. of T-2 toxin were killed at 1, 3, 6, 9, 12, 24 and 48 hr after treatment (HAT) and subjected to examination of the process of the development of T-2 toxin-induced apoptosis in the thymus and spleen. The early ultrastructural changes in lymphocytes characterized by shrinkage of the cell body and condensation of nuclear chromatin were detected at 3HAT in the thymus. The number of apoptotic lymphocytes observed by the in situ detection method for fragmented DNA increased drastically from 9 to 24 HAT in the thymus while it began to increase at 12 HAT in the spleen. The DNA ladder was first detected by agarose gel electrophoresis at 9 HAT and became clearer at 12 and 24 HAT in the thymus but was not clearly detected in the spleen throughout the observation period. Thus T-2 toxin-induced apoptosis developed earlier and was apparently severer in the thymus than in the spleen. Apoptotic was first detected by electron microscopy, then by the in situ detection method for fragmented DNA, and finally by DNA agarose gel electrophoresis.


Functional Status Is Associated With 30-Day Potentially Preventable Hospital Readmissions After Inpatient Rehabilitation Among Aged Medicare Fee-for-Service Beneficiaries.
To determine the association between patients' functional status at discharge from inpatient rehabilitation and 30-day potentially preventable hospital readmissions. A secondary objective was to examine the conditions resulting in these potentially preventable readmissions. Retrospective cohort study. Inpatient rehabilitation facilities submitting claims to Medicare. National cohort (N=371,846) of inpatient rehabilitation discharges among aged Medicare fee-for-service beneficiaries in 2013 to 2014. The average age was 79.1±7.6 years. Most were women (59.7%) and white (84.5%). Not applicable. (1) Observed rates and adjusted odds of 30-day potentially preventable hospital readmissions after inpatient rehabilitation and (2) primary diagnoses for readmissions. The overall rate of any 30-day hospital readmission after inpatient rehabilitation was 12.4% (n=46,265), and the overall rate of potentially preventable readmissions was 5.0% (n=18,477). Functional independence was associated with lower observed rates and adjusted odds ratios for potentially preventable readmissions. Observed rates for the highest versus lowest quartiles within each functional domain were as follows: self-care: 3.4% (95% confidence interval [CI], 3.3-3.5) versus 6.9% (95% CI, 6.7-7.1), mobility: 3.3% (95% CI, 3.2-3.4) versus 7.2% (95% CI, 7.0-7.4), and cognition: 3.5% (95% CI, 3.4-3.6) versus 6.2% (95% CI, 6.0-6.4), respectively. Similarly, adjusted odds ratios were as follows: self-care: .70 (95% CI, .67-.74), mobility: .64 (95% CI, .61-.68), and cognition: .84 (95% CI, .80-.89). Infection-related conditions (44.1%) were the most common readmission diagnoses followed by inadequate management of chronic conditions (31.2%) and inadequate management of other unplanned events (24.7%). Functional status at discharge from inpatient rehabilitation was associated with 30-day potentially preventable readmissions in our sample of aged Medicare beneficiaries. This information may help identify at-risk patients. Future research is needed to determine whether follow-up programs focused on improving functional independence will reduce readmission rates.


A type IV modification dependent restriction nuclease that targets glucosylated hydroxymethyl cytosine modified DNAs.
The Escherichia coli CT596 prophage exclusion genes gmrS and gmrD were found to encode a novel type IV modification-dependent restriction nuclease that targets and digests glucosylated (glc)-hydroxymethylcytosine (HMC) DNAs. The protein products GmrS (36 kDa) and GmrD (27 kDa) were purified and found to be inactive separately, but together degraded several different glc-HMC modified DNAs (T4, T2 and T6). The GMR enzyme is able to degrade both alpha-glucosy-HMC T4 DNA and beta-glucosyl-HMC T4 DNA, whereas no activity was observed against non-modified DNAs including unmodified T4 cytosine (C) DNA or non-glucosylated T4 HMC DNA. Enzyme activity requires NTP, favors UTP, is stimulated by calcium, and initially produces 4 kb DNA fragments that are further degraded to low molecular mass products. The enzyme is inhibited by the T4 phage internal protein I* (IPI*) to which it was found to bind. Overall activities of the purified GmrSD enzyme are in good agreement with the properties of the cloned gmr genes in vivo and suggest a restriction enzyme specific for sugar modified HMC DNAs. IPI* thus represents a third generation bacteriophage defense against restriction nucleases of the Gmr type.


Protective Effects of Arabinogalactan-Peptide Isolated from Wheat Flour against Myocardial Injury in an Ischemia/Reperfusion Rat Model.
We have previously shown that supplementation of wheat with hot-water extract reduces myocardial injury by inhibiting apoptosis in a rat model of myocardial infarction (MI). Arabinogalactan-peptide (AGP), a cell wall polysaccharide of wheat, was also responsible for the protection. However, the underlying mechanisms were not elucidated. In this study, we investigated the underlying mechanisms for how AGP supplementation reduces myocardial injury. First, we isolated highly pure AGP from all-purpose wheat flour. We supplemented rats with AGP at a dose of 100 mg/kg/d for 3 days, and subjected the rats to ischemia (30 min) through ligation of the left anterior descending coronary artery followed by reperfusion (3 h) through a release of the ligation. Supplementation with AGP significantly reduced the infarct size in the heart. In addition, AGP intake inhibited the apoptotic cascade, determined through decreased mitogen-activated protein kinases (p38 and c-Jun N-terminal kinase) phosphorylation, decreased Bcl-2-associated X protein/B-cell lymphoma ratios, and decreased generation of nicked DNA, which was confirmed through western blotting and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling staining. These findings indicate that AGP intake can protect against myocardial injury. Traditionally, consumption of dietary fiber such as AGP has been shown to reduce MI risk by inhibiting preocclusion steps through reducing risk factors. Our findings suggest that AGP intake can also reduce MI risk by inhibiting postocclusion steps. This study describes a better dietary recommendation and new prevention strategy for reducing MI risk through regular consumption of wheat rich in AGP.


Optimal Network-based Intervention in the Presence of Undetectable Viruses.
This letter presents an optimal control framework to reduce the spread of viruses in networks. The network is modeled as an undirected graph of nodes and weighted links. We consider the spread of viruses in a network as a system, and the total number of infected nodes as the state of the system, while the control function is the weight reduction leading to slow/reduce spread of viruses. Our epidemic model overcomes three assumptions that were extensively used in the literature and produced inaccurate results. We apply the optimal control formulation to crucial network structures. Numerical results show the dynamical weight reduction and reveal the role of the network structure and the epidemic model in reducing the infection size in the presence of indiscernible infected nodes.


Screening and evaluation of active compounds in polyphenol mixtures by HPLC coupled with chemical methodology and its application.
An off-line high performance liquid chromatography (HPLC) coupled with chemical methods has been developed to evaluate antioxidant activity of 11 standard polyphenol compounds (SPCs) and vitamin C (Vc) in terms of radical scavenging abilities. The structure-activity relationships of each SPC were also discussed. SPCs showed different abilities in scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis-3-ethyl-benzthiazoline-6-sulphonate (ABTS+) and hydroxyl (OH) free radicals. Among SPCs, quercetin and kaempferol, as typical flavonoids, displayed the greatest radical-scavenging activities and even exhibited higher activity in OH radical removal ability than that of Vc. Furthermore, the proposed method was also applied to screening polyphenolic antioxidant components from Cichorium endivia L. (C. endivia) seed extract. The results indicated that cynarin in the extract was a more active compound to scavenge DPPH and ABTS+ radicals than chlorogenic acid, while chlorogenic acid had stronger capacity in scavenging OH free radicals.


Exploration and Validation of Potential Biomarkers and Therapeutic Targets in Ferroptosis of Asthma.
Asthma is a chronic inflammatory airway disease involving multiple mechanisms, of which ferroptosis is a form of programmed cell death. Recent studies have shown that ferroptosis may play a crucial role in the pathogenesis of asthma, but no specific ferroptosis gene has been found in asthma, and the exact mechanism is still unclear. The present study aimed to screen ferroptosis genes associated with asthma and find therapeutic targets, in order to contribute a new clue for the diagnosis and therapy of asthma. Ferroptosis-related differentially expressed genes (FR-DEGs) in asthma were selected by the GSE41861, GSE43696 and ferroptosis datasets. Next, the FR-DEGs were subjected by GO and KEGG enrichment, and the mRNA-miRNA network was constructed. Then, GSEA and GSVA enrichment analysis and Immune infiltration analysis were performed, followed by targeted drug prediction. Finally, the expression of FR-DEGs was confirmed using GSE63142 dataset and RT-PCR assay. We found 13 FR-DEGs by the GSE41861, GSE43696 and ferroptosis database. Functional enrichment analysis revealed that the 13 FR-DEGs were enriched in oxidative stress, immune response, ferroptosis, lysosome, necrosis, apoptosis etc. Moreover, our results revealed the mRNA-miRNA network of the FR-DEGs and identified candidate drugs. Also, immune infiltration revealed that ELAVL1, CREB5, CBR1 and NR1D2 are associated with the immune cells and may be potential targets in asthma. Finally, 10 FR-DEGs were validated by the GSE63142 database. It was verified that 7 FR-DEGs were differentially expressed by collecting asthma patients and healthy controls. This study ultimately identified 7 FR-DEGs for the diagnosis and therapy of asthma. These 7 FR-DEGs contribute to oxidative stress and immune responses. This study provides potential therapeutic targets and biomarkers for asthma patients, shedding further light on the pathogenesis of asthma as well as providing new insights into the treatment of asthma.


A Cross-Dehydrogenative Annulation Strategy towards Synthesis of Polyfluorinated Phenanthridinones with Copper.
The first cross-dehydrogenative annulation of (hetero)aromatic amides with polyfluoro(hetero)arenes is presented. This operationally simple oxidative annulation process is mediated by inexpensive copper salt, accommodates a wide range of substrates with exquisite chemo- and regioselectivity profile, and produces demanding polyfluorinated phenanthridinones in high yields (up to 92 %). Using alkenyl amides under identical conditions, the synthesis of polyfluorinated 2-quinolones has also been accomplished. Given the importance of fluorinated heterocycles in the pharmaceutical industry and drug discovery, this work is highly significant.


Efficacy of digital pupillometry for diagnosis of Horner syndrome.
To evaluate the efficacy of digital pupillometry in the diagnosis of anisocoria related to Horner syndrome in adult patients. Retrospective, observational, case control study. Nineteen patients with unilateral Horner syndrome (Horner group) and age-matched controls of 30 healthy individuals with normal vision and neither optic nerve dysfunction nor pupillary abnormalities were included. Pupillary light reflex (PLR) of the Horner group and controls were measured by a dynamic pupillometer (PLR-200; NeurOptics Inc., Irvine, USA). Minimal and maximal (min/max) pupil diameters, latency, constriction ratio, constriction velocity, dilation velocity, and total time taken by the pupil to recover 75% of maximal pupil diameter (T75) were noted. PLR were measured at baseline in both groups and at 30-45 minutes later after 0.5% apraclonidine (Iopidine®; Alcon Laboratories, Fort Worth, TX, USA) instillation in the Horner group. The PLR parameters in the affected eye and inter-eye difference before and after 0.5% apraclonidine instillation. In the Horner group, pupil diameters and T75 showed significant difference between the affected eye and unaffected contralateral eye at baseline (all P<0.00625). Compared to controls, inter-eye difference values of pupil diameters and T75 were significantly larger in the Horner group (all P<0.001). After 0.5% apraclonidine instillation, changes in pupil diameter and constriction ratio were significantly larger in the affected eye compared to the unaffected contralateral eye (all P<0.00625). The area under the receiver operating characteristic curves for diagnosing Horner syndrome were largest for baseline inter-eye difference in min/max pupil sizes (AUC = 0.975, 0.994), T75 (AUC = 0.838), and change in min/max pupil sizes after apraclonidine instillation (AUC = 0.923, 0.929, respectively). The diagnostic criteria for Horner syndrome relying on baseline pupillary measurements was defined as one of the two major findings; 1) smaller maximal pupil diameter in the affected eye with an inter-eye difference of > 0.5 mm, or 2) T75 > 2.61 seconds in the affected eye, which showed a sensitivity of 94.7% and specificity of 93.3%. The diagnostic accuracy of apraclonidine testing showed a sensitivity of 84.6% and specificity of 92.3%. Digital pupillometry is an objective method for quantifying PLR. Baseline inter-eye difference in maximal pupil sizes and dilation lag measured by T75 was equally effective in the diagnosis of Horner syndrome compared to the reversal of anisocoria after apraclonidine instillation.


Cryptococcal meningitis with severe visual and hearing loss and radiculopathy in a patient without immunodeficiency.
Cryptococcosis is an important cause of lymphocytic meningitis, especially but not necessarily in immunocompromised patients. We present the case of a 23-year-old man with a severe and rapid course of a cryptococcal meningoencephalitis, which led to visual and hearing loss, psychotic illness and radiculopathy. There was no evidence of immunodeficiency. Treatment with amphotericin B and flucytosine led to improvement of the symptoms but did not eradicate the micro-organisms from the cerebrospinal fluid (CSF). Maintenance therapy with fluconazole was necessary and led to improvement of the CSF pathology.


Intrauterine endotoxin-induced impairs pulmonary vascular function and right ventricular performance in infant rats and improvement with early vitamin D therapy.
High pulmonary vascular resistance (PVR), proximal pulmonary artery (PA) impedance, and right ventricular (RV) afterload due to remodeling contribute to the pathogenesis and severity of pulmonary hypertension (PH). Intra-amniotic exposure to endotoxin (ETX) causes sustained PH and high mortality in rat pups at birth, which are associated with impaired vascular growth and RV hypertrophy in survivors. Treatment of ETX-exposed pups with antenatal vitamin D (vit D) improves survival and lung growth, but the effects of ETX exposure on RV-PA coupling in the neonatal lung are unknown. We hypothesized that intrauterine ETX impairs RV-PA coupling through sustained abnormalities of PA stiffening and RV performance that are attenuated with vit D therapy. Fetal rats were exposed to intra-amniotic injections of ETX, ETX+vit D, or saline at 20 days gestation (term = 22 days). At postnatal day 14, pups had pressure-volume measurements of the RV and isolated proximal PA, respectively. Lung homogenates were assayed for extracellular matrix (ECM) composition by Western blot. We found that ETX lungs contain decreased α-elastin, lysyl oxidase, collagen I, and collagen III proteins (P < 0.05) compared control and ETX+vit D lungs. ETX-exposed animals have increased RV mechanical stroke work (P < 0.05 vs. control and ETX+vit D) and elastic potential energy (P < 0.05 vs. control and ETX+vit D). Mechanical stiffness and ECM remodeling are increased in the PA (P < 0.05 vs. control and ETX+vit D). We conclude that intrauterine exposure of fetal rats to ETX during late gestation causes persistent impairment of RV-PA coupling throughout infancy that can be prevented with early vit D treatment.


Assessment of heat pain perception in relation to vibration exposure.
The effect of vibration on thin unmyelinated sensory fibers was studied by perception threshold measurement of heat pain. The investigation was a cross-sectional study of 98 vibration-exposed and 53 non-vibration-exposed workers. Pain perception was determined by using the "Marstock" method. The perception threshold of contact heat induced pain was assessed by the method of limits. Quantified personal energy-equivalent vibration exposure was assessed for all subjects on a group basis. The cumulated lifetime equivalent frequency-weighted vibration exposure was estimated based on measurements according to ISO 5349. The mean heat perception threshold was 46.2 degrees C (SD 2.6 degrees C) for the right hand and 46.0 degrees C (SD 2.7 degrees C) for the left. The results showed no mean difference (left = 0.1 degree C, right = 0.6 degree C) in heat pain perception between vibration-exposed and non-exposed subjects. There was a high correlation between the right and left hand measurements (r = 0.81). The risk (rate ratio) for impairment was 1.02 (95% CI 0.81-1.30) for the right hand and 1.00 (95% CI 0.79-1.26) for the left. The results of the study did not indicate any impairment as assessed by an increased perception threshold for heat pain. The lack of an increased heat pain threshold among the vibration-exposed workers in our study cannot exclude a possible lesional somatosensory influence from the exposure, as the lesional effect may also be a lowering of the threshold. The multiple and unrelated percepts of thermal sensations imply that it is not legitimate to draw conclusions about the total status of the small calibre afferents when testing only the heat pain perception.


Construction of the free energy landscape of biomolecules via dihedral angle principal component analysis.
A systematic approach to construct a low-dimensional free energy landscape from a classical molecular dynamics (MD) simulation is presented. The approach is based on the recently proposed dihedral angle principal component analysis (dPCA), which avoids artifacts due to the mixing of internal and overall motions in Cartesian coordinates and circumvents problems associated with the circularity of angular variables. Requiring that the energy landscape reproduces the correct number, energy, and location of the system's metastable states and barriers, the dimensionality of the free energy landscape (i.e., the number of essential components) is obtained. This dimensionality can be determined from the distribution and autocorrelation of the principal components. By performing an 800 ns MD simulation of the folding of hepta-alanine in explicit water and using geometric and kinetic clustering techniques, it is shown that a five-dimensional dPCA energy landscape is a suitable and accurate representation of the full-dimensional landscape. In the second step, the dPCA energy landscape can be employed (e.g., in a Langevin simulation) to facilitate a detailed investigation of biomolecular dynamics in low dimensions. Finally, several ways to visualize the multidimensional energy landscape are discussed.


Enhanced thermoelectric performance of single-walled carbon nanotubes/polyaniline hybrid nanocomposites.
Hybrid nanocomposites containing carbon nanotubes (CNTs) and ordered polyaniline (PANI) have been prepared through an in situ polymerization reaction using a single-walled nanotube (SWNT) as template and aniline as reactant. TEM, SEM, XRD, and Raman analyses show that the polyaniline grew along the surface of CNTs forming an ordered chain structure during the SWNT-directed polymerization process. The SWNT/PANI nanocomposites show both higher electrical conductivity and Seebeck coefficient as compared to pure PANI, which could be attributed to the enhanced carrier mobility in the ordered chain structures of the PANI. The maximum electrical conductivity and Seebeck coefficient of composites reach 1.25 x 10(4) S m(-1) and 40 microV K(-1), respectively, and the maximum power factor is up to 2 x 10(-5) W m(-1) K(-2), more than 2 orders of magnitude higher than the pure polyaniline. This study suggests that constructing highly ordered chain structure is a novel and effective way for improving the thermoelectric properties of conducting polymers.


Reference values for pulmonary tissue volume, membrane diffusing capacity, and pulmonary capillary blood volume.
Pulmonary tissue volume (Vti), carbon monoxide diffusing capacity, membrane diffusing capacity, pulmonary capillary blood flow and pulmonary capillary blood volume were measured in ninety (54 men and 36 women) healthy lifetime nonsmokers using an inert gas rebreathing technique. Prediction equations were generated using multiple linear regressions with height and age as the independent variables. Normalizing the data by dividing by functional residual capacity eliminated all sex differences. In contrast to the other variables, normalized pulmonary tissue volume did not correlate with any of the independent variables tested. Therefore, an average normalized Vti value can be recommended as a reference value


Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response.
The complement system is a key component of the host immune response for the recognition and clearance of Streptococcus pneumoniae. In this study, we demonstrate that the amidase LytA, the main pneumococcal autolysin, inhibits complement-mediated immunity independently of effects on pneumolysin by a complex process of impaired complement activation, increased binding of complement regulators, and direct degradation of complement C3. The use of human sera depleted of either C1q or factor B confirmed that LytA prevented activation of both the classical and alternative pathways, whereas pneumolysin inhibited only the classical pathway. LytA prevented binding of C1q and the acute-phase protein C-reactive protein to S. pneumoniae, thereby reducing activation of the classical pathway on the bacterial surface. In addition, LytA increased recruitment of the complement downregulators C4BP and factor H to the pneumococcal cell wall and directly cleaved C3b and iC3b to generate degradation products. As a consequence, C3b deposition and phagocytosis increased in the absence of LytA and were markedly enhanced for the lytA ply double mutant, confirming that a combination of LytA and Ply is essential for the establishment of pneumococcal pneumonia and sepsis in a murine model of infection. These data demonstrate that LytA has pleiotropic effects on complement activation, a finding which, in combination with the effects of pneumolysin on complement to assist with pneumococcal complement evasion, confirms a major role of both proteins for the full virulence of the microorganism during septicemia.


Investigating diet and physical activity in Malaysia: education and family history of diabetes relate to lower levels of physical activity.
The National Health and Morbidity Survey (NHMS, 2011), estimates that the number of Malaysian adults suffering from type 2 diabetes has increased from 8.3 to 31.2% since 1996. This study is a preliminary investigation of possible factors contributing to this epidemic. Knowledge of diabetes, health locus of control, diet and exercise habits, as well as family history, education level and other demographic factors to better understand the correlates of risky and healthy behaviors. This was done as part of a larger initiative to improve prevention efforts. Questionnaires were completed by 770 individuals from three Malaysian states: Selangor, Penang, and Terengganu. Findings showed that people with better health knowledge and those who have a family history of type 2 diabetes were more likely to have healthy diets. Also, health knowledge related to lower alcohol consumption. Participants with diabetic family members, however, also reported higher levels of stress. Counterintuitively, higher educational levels, higher internal locus of control, better health knowledge, as well as a family history of diabetes all correlated with lower levels of physical activity. Thus, it is suggested that, while increasing health knowledge will be important in addressing the type 2 diabetes epidemic in Malaysia, especially in relation to diet, other cultural factors, specifically norms related to exercise and physical activity, also need to be addressed if the spread of type 2 diabetes is to be addressed over the long term.


Patterns of invasive growth in vitro. Human decidua graviditatis confronted with established human cell lines and primary human explants.
Human decidua graviditatis was used as a receptor tissue to demonstrate invasive properties of human cells in vitro. In the confrontation between decidua and established cell lines of tumors and of normal origin as well as primary explanted cells, we noted differences in the cells' interactions with decidual tissue. The two original tumor cell lines, HeLa (carcinoma) and AFi (sarcoma), and a spontaneously transformed lymphoblastoid cell line showed aggressiveness, i.e., invasion, rapid proliferation, injury, and destruction of the decidual tissue. Strain HeLa S3 and two established cell lines, FL (amnion) and Girardi Heart, which are regarded as transformed cells because of their increased mitotic rate and polyploidy, exhibited various degrees of aggressiveness but did not invade. Freshly explanted fetal lung and endometrium caused no injury to the receptor tissue and were included in the decidual tissue.


Prevalence of self-reported physically active adults--United States, 2007.
The report, 2008 Physical Activity Guidelines for Americans (2008 Guidelines), released in October by the U.S. Department of Health and Human Services, provides new guidelines for aerobic physical activity (i.e., activity that increases breathing and heart rate) and muscle strengthening physical activity. Under the 2008 Guidelines, the minimum recommended aerobic physical activity required to produce substantial health benefits in adults is 150 minutes of moderate-intensity activity per week, or 75 minutes of vigorous-intensity activity per week, or an equivalent combination of moderate- and vigorous-intensity physical activity. Recommendations for aerobic physical activity in the 2008 Guidelines differ from those used in Healthy People 2010 (HP2010) objectives, which call for adults to engage in at least 30 minutes of moderate-intensity activity, 5 days per week, or 20 minutes of vigorous-intensity activity, 3 days per week. To establish baseline data for the 2008 Guidelines and compare the percentage of respondents who reported meeting these guidelines with the percentage who reported meeting HP2010 objectives, CDC analyzed data from the 2007 Behavioral Risk Factor Surveillance System (BRFSS) survey. This report summarizes the results of that analysis, which indicated that, overall, 64.5% of respondents in 2007 reported meeting the 2008 Guidelines, and 48.8% of the same respondents reported meeting HP2010 objectives. Public health officials should be aware that, when applied to BRFSS data, the two sets of recommendations yield different results. Additional efforts are needed to further increase physical activity.


Phase computations and phase models for discrete molecular oscillators.
Biochemical oscillators perform crucial functions in cells, e.g., they set up circadian clocks. The dynamical behavior of oscillators is best described and analyzed in terms of the scalar quantity, phase. A rigorous and useful definition for phase is based on the so-called isochrons of oscillators. Phase computation techniques for continuous oscillators that are based on isochrons have been used for characterizing the behavior of various types of oscillators under the influence of perturbations such as noise. In this article, we extend the applicability of these phase computation methods to biochemical oscillators as discrete molecular systems, upon the information obtained from a continuous-state approximation of such oscillators. In particular, we describe techniques for computing the instantaneous phase of discrete, molecular oscillators for stochastic simulation algorithm generated sample paths. We comment on the accuracies and derive certain measures for assessing the feasibilities of the proposed phase computation methods. Phase computation experiments on the sample paths of well-known biological oscillators validate our analyses. The impact of noise that arises from the discrete and random nature of the mechanisms that make up molecular oscillators can be characterized based on the phase computation techniques proposed in this article. The concept of isochrons is the natural choice upon which the phase notion of oscillators can be founded. The isochron-theoretic phase computation methods that we propose can be applied to discrete molecular oscillators of any dimension, provided that the oscillatory behavior observed in discrete-state does not vanish in a continuous-state approximation. Analysis of the full versatility of phase noise phenomena in molecular oscillators will be possible if a proper phase model theory is developed, without resorting to such approximations.


An approach to enhance the conservation-compatibility of solar energy development.
The rapid pace of climate change poses a major threat to biodiversity. Utility-scale renewable energy development (>1 MW capacity) is a key strategy to reduce greenhouse gas emissions, but development of those facilities also can have adverse effects on biodiversity. Here, we examine the synergy between renewable energy generation goals and those for biodiversity conservation in the 13 M ha Mojave Desert of the southwestern USA. We integrated spatial data on biodiversity conservation value, solar energy potential, and land surface slope angle (a key determinant of development feasibility) and found there to be sufficient area to meet renewable energy goals without developing on lands of relatively high conservation value. Indeed, we found nearly 200,000 ha of lower conservation value land below the most restrictive slope angle (<1%); that area could meet the state of California's current 33% renewable energy goal 1.8 times over. We found over 740,000 ha below the highest slope angle (<5%)--an area that can meet California's renewable energy goal seven times over. Our analysis also suggests that the supply of high quality habitat on private land may be insufficient to mitigate impacts from future solar projects, so enhancing public land management may need to be considered among the options to offset such impacts. Using the approach presented here, planners could reduce development impacts on areas of higher conservation value, and so reduce trade-offs between converting to a green energy economy and conserving biodiversity.


Pathophysiology of the right ventricle in health and disease: an update.
The contribution of the right ventricle (RV) to cardiac output is negligible in normal resting conditions when pressures in the pulmonary circulation are low. However, the RV becomes relevant in healthy subjects during exercise and definitely so in patients with increased pulmonary artery pressures both at rest and during exercise. The adaptation of RV function to loading rests basically on an increased contractility. This is assessed by RV end-systolic elastance (Ees) to match afterload assessed by arterial elastance (Ea). The system has reserve as the Ees/Ea ratio or its imaging surrogate ejection fraction has to decrease by more than half, before the RV undergoes an increase in dimensions with eventual increase in filling pressures and systemic congestion. RV-arterial uncoupling is accompanied by an increase in diastolic elastance. Measurements of RV systolic function but also of diastolic function predict outcome in any cause pulmonary hypertension and heart failure with or without preserved left ventricular ejection fraction. Pathobiological changes in the overloaded RV include a combination of myocardial fibre hypertrophy, fibrosis and capillary rarefaction, a titin phosphorylation-related displacement of myofibril tension-length relationships to higher pressures, a metabolic shift from mitochondrial free fatty acid oxidation to cytoplasmic glycolysis, toxic lipid accumulation, and activation of apoptotic and inflammatory signalling pathways. Treatment of RV failure rests on the relief of excessive loading.


Design of a pragmatic trial in minority children presenting to the emergency department with uncontrolled asthma: The CHICAGO Plan.
Among children with asthma, black children are two to four times as likely to have an emergency department (ED) visit and die from asthma, respectively, compared to white children in the United States. Despite the availability of evidence-based asthma management guidelines, minority children are less likely than white children to receive or use effective options for asthma care. The CHICAGO Plan is a three-arm multi-center randomized pragmatic trial of children 5 to 11years old presenting to the ED with uncontrolled asthma that compares: [1] an ED-focused intervention to improve the quality of care on discharge to home, [2] the same ED-focused intervention together with a home-based community health worker (CHW)-led intervention, and [3] enhanced usual care. All children receive spacers for the metered dose inhaler and teaching about its use. The Patient-Reported Outcomes Measurement Information System (PROMIS) Asthma Impact Scale and Satisfaction with Participation in Social Roles at 6months are the primary outcomes in children and in caregivers, respectively. Other patient-reported outcomes and indicators of healthcare utilization are assessed as secondary outcomes. Innovative features of the CHICAGO Plan include early and continuous engagement of children, caregivers, the Chicago Department of Public Health, and other stakeholders to inform the design and implementation of the study and a shared research infrastructure to coordinate study activities. The objective of this report is to describe the development of the CHICAGO Plan, including the methods and rationale for engaging stakeholders, the shared research infrastructure, and other features of the pragmatic clinical trial design.


The Orinda Study.
The Orinda Study was the first interdisciplinary effort to establish the validity of a vision screening protocol and led to the development of the clinically based Modified Clinical Technique (MCT), a protocol that has been in widespread use for the past 24 years. This paper reviews the original thoughts behind the study and its accomplishments and assesses the impact of the study on vision screening. Future obligations of optometrists and other vision screeners are discussed in view of the past benefits of the study.


The relationship between nurses' perceived organisational, supervisor and coworker support, psychological well-being and job performance.
To examine the relationship involving nurses' perception of organisational, supervisor and co-worker support, psychological well-being and job performance. The cross-sectional, correlational study was conducted from June 2016 to January 2017 after approval from the ethics review committee of Istanbul Medipol University, Istanbul, Turkiye, and comprised nurses working in public or private sector and being in their current employment for at least one year. Data was obtained using Organisational Support, Co-Worker Support, Supervisor Support, Psychological Well-Being and Job Performance scales. Data was analyzed using SPSS 26. Of the 1056 nurses, 896(84.8%) were women and 160(15.2%) were men. The overall mean age was 30.69±7.53 years (range: 17-59 years) and mean professional experience was 9.31±7.66 years (range: 1-36 years). Organisational, supervisor and co-worker support increased psychological wellbeing. Supervisor and co-worker support had a positive effect on job performance, but organisational support did not. Psychological wellbeing also increased job performance. Psychological well-being had a mediating role in the effect of organisational, supervisor and co-worker support on job performance. There was a positive relationship between perceived support, psychological wellbeing and job performance of nurses.


[Anticoagulation therapy in pulmonary arterial hypertension].
Vascular thrombosis implicates in the pathogenesis of pulmonary arterial hypertension (PAH). Anticoagulation therapy (warfarin) has been recommended by many experts in the treatment of PAH. However, the long-term effectiveness of anticoagulation therapy remains controversial. Because of the various drugs, such as epoprostenol, bosentan, and sildenafil, for the treatment of PAH recently, warfarin alone is not a realistic therapy for PAH. Accordingly we reviewed the previous manuscript regarding anticoagulation therapy for PAH, and looked at the current role of anticoagulation therapy in Japan.


Serum sickness-like reactions.
A serum sickness-like reaction (SSLR) to drug administration usually consists of cutaneous rash, arthralgia/arthritis, and, often, fever. This entity rarely has been discussed in the dermatologic literature. We describe the case of a 3-year-old girl with urticaria, fever, and arthralgia that appeared 8 days after starting cefaclor therapy for otitis media.


Understanding equality in health care: a Christian free-market approach.
This paper examines the arguments presented by the Roman Catholic Bishops in their 1993 Pastoral Resolution, Comprehensive Health Care Reform: Protecting Human Life, Promoting Human Dignity, Pursuing the Common Good, concerning health care reform. Focusing on the meaning of equality in health care and traditional Roman Catholic doctrine, it is argued that the Bishops fail to grasp the force of the differences among persons, the value of the market, and traditional scholastic arguments concerning obligatory and extraordinary health care. To attempt to equalize the distribution of health care would be ruinous. A more traditional understanding of Christian thought reveals an acceptance of inequality in health care distribution and a bias against using the secular state to coerce a solution to such concerns for social justice.


Time Window of the Critical Period for Neuroplasticity in S1, V1, and A1 Sensory Areas of Small Rodents: A Systematic Review.
The plasticity of the central nervous system (CNS) allows the change of neuronal organization and function after environmental stimuli or adaptation after sensory deprivation. The so-called critical period (CP) for neuroplasticity is the time window when each sensory brain region is more sensitive to changes and adaptations. This time window is usually different for each primary sensory area: somatosensory (S1), visual (V1), and auditory (A1). Several intrinsic mechanisms are also involved in the start and end of the CP for neuroplasticity; however, which is its duration in S1, VI, and A1? This systematic review evaluated studies on the determination of these time windows in small rodents. The careful study selection and methodological quality assessment indicated that the CP for neuroplasticity is different among the sensory areas, and the brain maps are influenced by environmental stimuli. Moreover, there is an overlap between the time windows of some sensory areas. Finally, the time window duration of the CP for neuroplasticity is predominant in S1.


Hemorheologic alterations induced by incremental treadmill exercise in thoroughbreds.
Hemorheologic alterations induced by incremental treadmill exercise were examined in 5 Thoroughbreds. Blood viscosity; PCV; RBC filterability, density gradient profile, and shape; serum and RBC electrolyte concentrations; and plasma total solids and lactate concentrations were measured before exercise, at treadmill speeds of 9 and 13 m/s, and 10 minutes after exercise. Exercise was associated with significant (P < 0.05) increases in PCV, blood viscosity, and plasma total solids concentration. After adjustment of PCV to 40% by adding or removing each horse's own plasma, blood viscosity remained significantly greater in the sample obtained at 13 m/s, compared with that in samples taken at rest. Filterability of RBC was significantly decreased at 13 m/s, compared with values from other sampling times. During exercise, a significantly greater proportion of the RBC were less dense and were found in the upper layers of the RBC density gradient profile, compared with resting values. This change was associated with a significant increase in RBC mean cell volume. Rapid increases in serum sodium and potassium concentrations during exercise were accompanied by significant increases in RBC potassium and chloride concentrations. This study revealed a consistent pattern of hemorheologic alterations associated with exercise in Thoroughbreds, suggesting that multiple hemorheologic tests are needed to adequately define these complex alterations during exercise in horses.


Development of video-assisted breast cancer surgery: Initial experience with a novel method for creating working space without prior liposuction.
Endoscopic techniques are promising in breast surgery. In order to create working space, liposuction is widely used in video-assisted breast surgery (VABS). However, the use of liposuction is likely associated with side effects that may partly limit the application of VABS. Therefore, a new technique of endoscopic axillary lymphadenectomy without prior liposuction was developed by our group. A total of 106 female patients underwent VABS, with special adaptation of the video-assisted surgical procedures previously described. Differing from other endoscopic surgery techniques, our adaptations of VABS included the selection of the working instruments, trocar placement, creation of working space, order of axillary lymph node dissection and method of mastectomy. The operative time was 50-180 min (mean, 85.5 min). The intraoperative blood loss ranged from 20 to 100 ml (mean, 48 ml). The mean lymph node number harvested was 11.5 (range, 6-31). No serious intra- or postoperative complications were recorded. There was no axillary tumor relapse, trocar site tumor implantation or upper limb edema. Without prior liposuction, our new technique of VABS reduced the blood loss volume, endoscopic surgery time, total volume of drainage fluid and, most importantly, the risk of port-site metastases. This new technique appears to have great clinical potential and good prospects for future endoscopic breast surgery development.


Two cases of solitary fibrous tumor/hemangiopericytoma with different clinical features according to the World Health Organization classification: case report and review of the literature.
Solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) have been classified as one entity by the World Health Organization in 2016 due to gene fusion between NAB2 and STAT6. In the Central Nervous System (CNS), a hypocellular, collagenized tumor with a classic SFT phenotype is considered grade I, whereas more densely cellular tumors mostly corresponding to the HPC phenotype are classified as grade II or III (anaplastic) depending in mitotic count (<5 vs. >5 mitoses per 10 high-power fields). Herein, we report two cases of targeted SFT/HPC in which pathological differences and WHO grading affect clinical features. A 75-year-old woman presented with headache and had an intradural extramedullary tumor at the C1 to C2 level. The tumor was well-circumscribed and attached only to the dura mater. It was totally removed and diagnosed SFT/HPC grade I. In contrast, a 68-year-old woman presented with numbness in the right upper limb and had an intradural extramedullary tumor at the medulla to C3 levels The tumor was irregularly marginated and strongly adherent to the spinal cord and involved the vertebral artery. It was sub totally removed and diagnosed SFT/HPC grade II. To the best of our knowledge, there are only 12 cases of SFT/HPC at the craniocervical junction, including the present two cases, of which four that were adherent to the spinal cord or involved the vertebral artery were grade II or III. Although the location of the tumor was almost the same, there were significant differences in the intraoperative findings according to the WHO grading.


Community dynamics of subgingival microbiome in periodontitis and targets for microbiome modulation therapy.
The microbial aetiology for periodontitis has been widely studied and deciphered for more than a century. The evolving and changing concepts about periodontal microbiology can be attributed to continuously developing laboratory techniques. The current sequencing platforms have not only expanded the catalog of periodontal pathogens but have also facilitated the understanding of functional interactions of the ecological framework. However, the translation of this new knowledge to advance periodontal therapeutics is minimal. We contend that novel clinical interventions directed beyond conventional therapies need to be emphasized. A clear understanding of the structural and functional dynamics of subgingival microbiota is a pre-requisite for developing any microbiome-based interventions for applications in periodontal health care. In this review, we discuss the 16 s-rRNA gene sequencing-based knowledge of the subgingival microbial community structure, its interactions and functions, and our perspective on the potential to engineer it for periodontal therapeutics. Harnessing this next-generation sequencing-based knowledge, microbiome modulation therapies are poised to change microbiome therapeutics' face.


Effect of chin tuck against resistance exercise on patients with dysphagia following stroke: A randomized pilot study.
Recently, chin tuck against resistance exercise (CTAR) has been reported as a remedial treatment for pharyngeal dysphagia. However, the clinical evidence of the effect is still lacking. This study investigated the effect of CTAR on the swallowing function in patients with dysphagia following subacute stroke. The patients were randomly assigned to an experimental (n = 11) or a control group (n = 11). The experimental group performed CTAR using the CTAR device. The control group received only conventional dysphagia treatment. Both groups received training on five days a week, for four weeks. The swallowing function was measured using functional dysphagia scale (FDS) and penetration-aspiration scale (PAS), based on a videofluoroscopic swallowing study (VFSS). The experimental group showed more improvements in the oral cavity, laryngeal elevation/epiglottic closure, residue in valleculae, and residue in pyriform sinuses of FDS and PAS compared to the control group (p < 0.05, all). This study demonstrated that CTAR is effective in improving the pharyngeal swallowing function in patients with dysphagia after stroke. Therefore, we recommend CTAR as a new remedial training alternative to HLE.


Takotsubo syndrome: hyperthyroidism, pheochromocytoma, or both? A case report.
Takotsubo syndrome (TTS) is a transient left ventricular dysfunction usually with apical akinesia (classical pattern). Other less frequent variants have been described: the mid-ventricular pattern is characterized by hypokinesia of the mid-left ventricle and hypercontractile apical and basal segments; the inverted or basal pattern is characterized by basal and mid-ventricular segment hypokinesia or akinesia with preserved contractility or hypercontractility of apical segments and finally the focal pattern. There are also biventricular variants and forms with exclusive involvement of the right ventricle. There is a correlation between endocrine disorders and TTS, the one most frequently described is with pheochromocytoma. Catecholamine-mediated myocarditis, focal and diffuse myocardial fibrosis, and myocardial dysfunction are described in pheochromocytoma. We describe a case of a 69-year-old patient with a recent diagnosis of hypertension and Graves' disease, hospitalized for persistent chest pain, hypertensive crisis, tachycardia, dyspnoea, and diaphoresis. Thyroid hormones, antibodies to TSH receptors, and hs-troponin I were increased. Electrocardiogram showed sinus tachycardia at 130 b.p.m., first-degree atrioventricular block, signs of left ventricular hypertrophy with inverted T wave in V4-V6. Echocardiogram demonstrated left ventricular apical and para-apical akinesia. Coronary angiography ruled out an obstructive coronary artery disease. Computed tomography angiogram aortic dissection ruled out aortic dissection but incidentally revealed a left adrenal mass compatible with a pheochromocytoma. Plasma and urinary metanephrines were increased. A TTS secondary to pheochromocytoma and hyperthyroidism was diagnosed. Pharmacological treatment included nitrates, urapidil and esmolol IV and methimazole at high doses. Type 2 multiple endocrine neoplasia has been excluded. After a complete haemodynamic stability on 20th day of hospitalization, the patient underwent an adrenalectomy. High levels of catecholamines in pheochromocytoma can lead to myocardial dysfunction. Similarly, an excess of thyroid hormones with up-regulation of adrenergic system can lead to myocardial dysfunction. These two conditions, if both present, define a high haemodynamic risk profile. How do catecholamines interact with the thyroid gland? The clinical case is of interest as a relationship has been hypothesized between the incretion of plasma catecholamines and Graves' disease. We suppose an imbalance of the immune system with a predominance of the T helper-type 2 (Th2)-mediated response. Predominance of Th2-mediated immune response may induce humoral immunity causing Graves' disease. In addition Th2 cytokines are strong inducers of M2 macrophages (alternatively activated) that are involved in autoimmune diseases, myocarditis, and myocardial fibrosis. Knowing the interaction between the cardiovascular system, immune response, and endocrine glands can help define the patient's risk class, possible complications, and follow-up.


Quantitative morphology of human retrolaminar optic nerve vasculature.
To quantify the variation in the blood supply of the retrolaminar optic nerve in humans. The retrolaminar anterior optic nerve is supplied by an elliptical arterial "circle" of Haller and Zinn formed by anastomoses around the optic nerve between medial and lateral paraoptic short posterior ciliary arteries (PO-SPCAs). The frequency with which complete perioptic nerve arteriolar anastomoses (PONAA) occur is unknown, yet they form the basis for many postulated pathophysiological mechanisms. Scanning electron microscopy was performed on 25 orbital and ocular microvascular corrosion casts (methyl methacrylate) from 20 human cadavers of subjects 21 to 97 years of age without known ocular disease. Eighteen casts were examined in detail after microdissection (the analysis of seven casts was limited because of their fragility). In 15/18 (83%) casts, the PONAA were supplied by branches of a medial and lateral PO-SPCA; in 2/18, they were supplied by one (lateral) PO-SPCA; and in 1/18, they were supplied by a superior PO-SPCA and two horizontal PO-SPCAs. The PONAA had intact superior and inferior anastomoses in 8/18 (44%) casts, anastomoses with narrowed portions in 6/18 (33%), and incomplete in 4/18 (23%). Narrowed portions were not preferentially distributed to either superior or inferior anastomoses. Complete PONAA was found in more than 75% of casts, including anastomoses with narrow portions in 33% of casts.


PIASy represses TRIF-induced ISRE and NF-kappaB activation but not apoptosis.
The TIR domain-containing adapter protein TRIP is critically involved in TLR3-induced IFN-beta production through activation of NF-kappaB and ISRE. In addition, TRIF also induces apoptosis when overexpressed in 293 cells. In this report, we demonstrate that PIASy, a member of the PIAS SUMO-ligase family, interacts with TRIP, IRF-3 and IRF-7. In reporter gene assays, PIASy dramatically inhibits TRIF-induced NF-kappaB, ISRE and IFN-beta activation but not TRIF-induced apoptosis. Furthermore, PIASy also inhibits IRF-3, IRF-7 and Sendai virus-induced ISRE activation. Our results suggest that PIASy is an inhibitor of TRIF-induced ISRE and NF-kappaB activation but not apoptosis.